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Use of relaxin treat diseases related to vasoconstriction

a technology of vasodilation and relaxin, which is applied in the direction of anti-cancer medical ingredients, peptide/protein ingredients, and therapy, can solve the problems of reducing cardiac output and other problems, and achieve the effects of safe and effective relaxation, increased vasodilation, and beneficial therapeutic effects

Inactive Publication Date: 2004-04-20
RUTGERS THE STATE UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

An advantage of the present invention lies in the fact that the safety profile of relaxin in humans is superior to other agents, such as VEGF and FGF.
lies in the fact that the safety profile of relaxin in humans is superior to other agents, such as VEGF and FGF.
A further advantage of the use of relaxin to treat hypertensive vascular diseases is that it is effective in both males and females.
Another object of the invention is a method whereby therapeutically effective amounts of relaxin are repeatedly administered to a patient over a period of time to obtain a beneficial therapeutic result.
Another aspect of the invention is to repeatedly or substantially continuously administer relaxin over a period of time in a manner so as to maintain therapeutic blood levels of relaxin over periods sufficient to obtain therapeutic results.
A feature of the invention is injectable and sustained-release formulations of relaxin which are useful in the method of the invention wherein the formulation comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of relaxin.

Problems solved by technology

Vasoconstriction, or the reduction in the cross-sectional area of the lumen of small blood vessels, is a potentially lethal condition arising in a variety of pathologies, and is due either to vasospasm, inadequate vasodilation, thickening of the vessel wall, or the accumulation of flow-restricting materials on the internal wall surfaces or within the wall itself.
However, negative consequences, such as hypotension, tachycardia and reduced cardiac output have been observed when VEGF is given to patients.

Method used

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  • Use of relaxin treat diseases related to vasoconstriction
  • Use of relaxin treat diseases related to vasoconstriction
  • Use of relaxin treat diseases related to vasoconstriction

Examples

Experimental program
Comparison scheme
Effect test

example 1

Relaxin is a Potent Renal Vasodilator in Conscious Rats

Materials and Methods

Animal Preparation

Long-Evans female rats aged 10-14 weeks were purchased from Harlan Sprague-Dawley (Frederick, Md.). They were fed PROLAB RMH 2000 diet containing 0.48% sodium (PME Feeds Inc., St. Louis, Mo.) and provided water ad libitum. To prepare the rats for experimental procedures, they were trained for several hours in a Plexiglas restraining cage (Braintree Scientific Co., Braintree, Mass.) on at least five different occasions before surgical intervention. These cages afforded sufficient space for grooming of the face and front paws while preventing the rat from turning around. Thus, accurate timed-urine collections and blood samplings were made possible from the chronically implanted bladder and vascular catheters, respectively. Rats failing to habituate to the cage were eliminated from the study (<1%). All animal procedures were approved by the Institutional Animal Care and Use Committee of the Ma...

example 2

Impact of Gender and Endothelin on Renal Vasodilation and Hyperfiltration Induced by Relaxin in Conscious Rats

Methods

Animal preparation.

Long Evans female and male rats of 10-14 weeks of age were used. Those animals studied at the University of New Mexico were purchased from Harlan Sprague-Dawley (Indianapolis, Ind.) and were fed PROLAB RMH 2500 diet containing 0.40% sodium (PME Feeds Inc., St. Louis, Mo.). The rats investigated at the Magee-Womens Research Institute were purchased from Harlan Sprague-Dawley (Frederick, Md.) and they were fed PROLAB RMH 2000 diet containing 0.48% sodium (PME Feeds Inc., St. Louis Mo.). The rats were maintained on a 12 hour light / dark cycle in fully accredited Animal Resource Facilities approved by the Association for Assessment and Accreditation of Laboratory Animal Care. All experiments were approved by the Institutional Animal Care and Use Committee of the University of New Mexico School of Medicine or the Magee-Womens Research Institute.

Prior to s...

example 3

Systemic Relaxin Administration Stimulates Angiogenic / Vasodilatory Cytokine Expression and Vesselformation in a Rat Myocardial Infarct Model.

Female Sprague Dawley rats, approximately 12-weeks of age were used. Rats were anesthetized by intraperitoneal (i.p.) injection of up to 1 ml / kg ketamine / medetomidine (6:4). Following exteriorization of the heart, the left coronary artery was ligated near its origin with a silk suture. In sham surgery control animals, the suture was placed superficially into the muscle adjacent to the coronary artery. Post-closure EKG's were monitored for S-T segment elevation in LCAL animals to confirm the outcome of ligation. Immediately following cardiac surgery, a primed mini-osmotic pump containing relaxin or vehicle (20 mM acetate, pH 5.0) was aseptically implanted into a subcutaneous (s.c.) pocket on the dorsal interscapular region. Vehicle or relaxin (0.1 mg / kg / day) was delivered as a continuous s.c. infusion for 7 or 21 days to either sham or LCAL anim...

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Abstract

The invention related to methods of treating disease related to vasoconstriction that is a major factor in hypertensive vascular diseases and vasodilation, generally comprising administering to an individual an effective amount of a pharmaceutically active relaxin. Relaxin functions to increase both vasodilation and angiogenesis in males as well as females, and is useful in treating a wide variety of diseases relating to vasoconstriction.

Description

This invention is in the field of diseases related to vasoconstriction, and in particular to the use of relaxin to treat diseases related to vasoconstriction.Vasoconstriction, or the reduction in the cross-sectional area of the lumen of small blood vessels, is a potentially lethal condition arising in a variety of pathologies, and is due either to vasospasm, inadequate vasodilation, thickening of the vessel wall, or the accumulation of flow-restricting materials on the internal wall surfaces or within the wall itself. Vasoconstriction is a major factor in various hypertensive vascular diseases, as well as conditions which result from such diseases, including progressive generalized atherogenesis, myocardial infarct, stroke, hypertension, glaucoma, migraine, ischemia, and diabetes mellitus, among others.Hypertension produced by renal disease is generally the result of either an alteration in the renal handling of sodium and fluids leading to volume expansion or an alteration in renal...

Claims

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Application Information

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IPC IPC(8): A61K38/22
CPCA61K38/2221A61P9/10A61P9/12
Inventor CONRAD, KIRK P.LEWIS, MARTYNUNEMORI, ELAINE N.HUANG, XINFANTOZZI, CAROL A.
Owner RUTGERS THE STATE UNIV
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